1,400 research outputs found

    Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

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    Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

    Combined palaeolimnological and ecological approach provides added value for understanding the character and drivers of recent environmental change in Flow Country lakes

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    The Flow Country peatlands receive national and international recognition and protection as a highly valued habitat, and also provide a number of important ecosystem services. While there has been much research on the terrestrial peatland habitat of the Flow Country, the area’s many hundreds of natural water bodies have been largely unstudied. The first part of this study therefore focuses on establishing the contemporary conditions at 18 Flow Country lakes, examining between-lake heterogeneity in terms of physical structure, water chemistry and biological communities. Temporal change in these lakes is then considered by combining contemporary ecological and palaeolimnological approaches. We examine how the diatom and chironomid communities of Flow Country lakes have changed since a time prior to the mid-nineteenth century. Results show that the lake communities today are different to those present pre-1850, containing more taxa tolerant of increased acidity and nutrient availability. General linear modelling (GLM) analysis demonstrated a statistically significant association between the extent of change in diatom communities and both dissolved organic carbon (DOC) and nitrate. Community shifts, though considerable, are shown to be complex and idiosyncratic and no shift between trophic states is indicated. The extent and type of coarse-scale community change we observed points to widespread bottom-up drivers such as land management, afforestation and/or atmospheric deposition rather than more localised management practices such as fish stocking. The benefits of combining approaches is discussed and palaeolimnological methods by which land management, afforestation and atmospheric deposition could be further disentangled are identified

    Borrowing from the palaeolimnologists toolkit; the use of lake sediment cores in diagnosing the causes of freshwater species decline

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    Populations of freshwater species are experiencing dramatic declines globally. Tools that facilitate the diagnosis of decline and identify management solutions and/or restoration targets are thus vital. Typically approaches taken to diagnose decline are carried out over short timescales and rely upon identifying spatial associations between presence or abundance of declining species and variables hypothesised to be driving decline. The potential to contextualise observed declines on longer time scales, with a broader range of potential explanatory variables is frequently dismissed, because of a perceived lack of existing long-term data. In this study we explore the value of incorporating a longer-term perspective to decline diagnosis using the common scoter as a case study. The number of scoter breeding in Scotland has declined substantially since the 1970s. Hypotheses for decline include a reduction in macroinvertebrate food available for females and young at the breeding lakes. In this study we apply palaeolimnological techniques to generate standardised, long-term ecological data, enabling us to characterise recent changes at four common scoter breeding lakes. Our results demonstrate that the (macroinvertebrate) food resource of common scoter has, in fact, gradually increased in abundance at all four sites from ca. 1900, and that a further statistically significant increase in macroinvertebrate abundance occurred at ca. 1970. We draw on our palaeolimnological data, to explore alternative hypotheses for common scoter decline. Increases in overall abundance across multiple algal, macrophyte and macroinvertebrate taxa, combined with specific increases in nutrient tolerant taxa, and concurrent declines in nutrient sensitive taxa indicate that the lakes have experienced enrichment within their current oligotrophic state during the last 100 years, and that this trajectory has become more marked during the period of common scoter decline. There is no evidence of changes to habitat, turbidity or increased competition from fish. In the absence of within lake changes that could be detrimental to the benthic (and generalist) feeding common scoter, we conclude that factors outside of the lake, such as increased predation, associated with afforestation in the surrounding area, are the most plausible drivers of common scoter decline. Prioritisation/testing of management solutions that address these issues are indicated

    Exceptional twentieth-century slowdown in Atlantic Ocean overturning circulation

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    Possible changes in Atlantic meridional overturning circulation (AMOC) provide a key source of uncertainty regarding future climate change. Maps of temperature trends over the twentieth century show a conspicuous region of cooling in the northern Atlantic. Here we present multiple lines of evidence suggesting that this cooling may be due to a reduction in the AMOC over the twentieth century and particularly after 1970. Since 1990 the AMOC seems to have partly recovered. This time evolution is consistently suggested by an AMOC index based on sea surface temperatures, by the hemispheric temperature difference, by coral-based proxies and by oceanic measurements. We discuss a possible contribution of the melting of the Greenland Ice Sheet to the slowdown. Using a multi-proxy temperature reconstruction for the AMOC index suggests that the AMOC weakness after 1975 is an unprecedented event in the past millennium (p > 0.99). Further melting of Greenland in the coming decades could contribute to further weakening of the AMOC

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Moment Closure - A Brief Review

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    Moment closure methods appear in myriad scientific disciplines in the modelling of complex systems. The goal is to achieve a closed form of a large, usually even infinite, set of coupled differential (or difference) equations. Each equation describes the evolution of one "moment", a suitable coarse-grained quantity computable from the full state space. If the system is too large for analytical and/or numerical methods, then one aims to reduce it by finding a moment closure relation expressing "higher-order moments" in terms of "lower-order moments". In this brief review, we focus on highlighting how moment closure methods occur in different contexts. We also conjecture via a geometric explanation why it has been difficult to rigorously justify many moment closure approximations although they work very well in practice.Comment: short survey paper (max 20 pages) for a broad audience in mathematics, physics, chemistry and quantitative biolog
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